Lipid bilayer composition influences small multidrug transporters
Lipid bilayer composition influences small multidrug transporters
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DOI：
10.1186/1471-2091-9-31
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发表时间：
2008-11-25
期刊：
影响因子：
--
通讯作者：
Booth, Paula J.
中科院分区：
文献类型：
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作者：
Charalambous, Kalypso;Miller, David;Booth, Paula J.
背景：膜蛋白受其周围脂质的影响。我们调查的双层组合物的膜转运活性的两个成员的小的多药耐药家族的大肠杆菌转运，EmrE和结核分枝杆菌，TBSMR的影响。我们特别讨论了磷脂酰乙醇胺和阴离子脂质对这些多药物转运蛋白活性的影响。磷脂酰乙醇胺脂质是两种转运蛋白的膜天然的，并且也改变脂质双层的侧压分布。脂质双层的侧压力影响膜蛋白的插入，折叠和活动，并已被证明会影响重构，拓扑结构和活动的膜转运proteins.Results：EmrE和TBsmr被发现表现出类似的依赖于脂质组合物，磷脂酰乙醇胺增加甲基紫精运输。阴离子脂质也增加运输EmrE和TBsmr，与蛋白质表现出的偏好，其最普遍的天然阴离子脂质头基;磷脂酰甘油EmrE和磷脂酰肌醇TBsmr.Conclusion：这些研究结果表明，膜的物理状态修改药物转运和底物易位是依赖于在体外脂质组合物。多药转运活性似乎响应于双层对转运蛋白施加的侧向力的改变。
Background: Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins.Results: Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr.Conclusion: These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer.